18113-07-0|4-Chloro-3-methoxyphenol| Ambeed

CAS No. :	18113-07-0
Formula :	C₇H₇ClO₂
M.W :	158.58
SMILES Code :	OC1=CC=C(Cl)C(OC)=C1
MDL No. :	MFCD16998742
InChI Key :	NKFRBXPBRPYULV-UHFFFAOYSA-N
Pubchem ID :	11099860

Safety of [ 18113-07-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319
Precautionary Statements:	P305+P351+P338

Computational Chemistry of [ 18113-07-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.14
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	39.97
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	29.46 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.71
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.36
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.05
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.75
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.98
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.97

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.69
Solubility	0.325 mg/ml ; 0.00205 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.62
Solubility	0.381 mg/ml ; 0.00241 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.55
Solubility	0.444 mg/ml ; 0.0028 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.59 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.46

Application In Synthesis of [ 18113-07-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 18113-07-0 ]

[ 18113-07-0 ] Synthesis Path-Downstream 1~54

1
[ 61638-01-5 ]
[ 18113-07-0 ]

References: [1]Biochemical Journal,1949,vol. 45,p. 381,383.

2
[ 18113-07-0 ]
[ 98-59-9 ]
4-chloro-3-methoxyphenyl 4-methylbenzenesulfonate [ No CAS ]

References: [1]Biochemical Journal,1949,vol. 45,p. 381,383.

3
[ 18113-07-0 ]
[ 77-78-1 ]
[ 7051-13-0 ]

References: [1]Justus Liebigs Annalen der Chemie,1914,vol. 405,p. 276.

4
[ 13726-14-2 ]
[ 18113-07-0 ]

References: [1]Justus Liebigs Annalen der Chemie,1914,vol. 405,p. 276.
[2]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

5
[ 3068-88-0 ]
[ 18113-07-0 ]
[ 111478-42-3 ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2169 - 2177.

6
[ 3724-65-0 ]
[ 18113-07-0 ]
[ 111478-41-2 ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2169 - 2177.

7
[ 150-19-6 ]
[ 18113-07-0 ]

Yield	Reaction Conditions	Operation in experiment
46%	With N-chloro-succinimide; In acetonitrile; at 0 - 20℃; for 2h;Heating / reflux;	Example 3. 2-(4-Chloro-3-methoxy-phenoxymethyl)-l-(3,5-dichloro-benzyI)-lH- imidazoleTo a solution of 3-methoxyphenol (621 mg, 5.0 mmol) in dry acetonitrile (10 mL) at O0C was added N-chlorosuccinimide. The reaction was allowed to warm to ambient temperature then heated at reflux for 2 h. TLC analysis (4:1, hexanes/EtOAc) indicated two products (Rf: 0.22 and 0.30). After removal of solvent in vacuo and column chromatography (8:1 to 4:1 hexanes/EtOAc) the two products were isolated individually and characterized by 1H and NuOESY NuMR. The desired 4-chloro-3-methoxyphenol was identified as the lower Rf product and isolated as a colorless oil (360 mg, 46%).

References: [1]Patent: WO2006/107923,2006,A1 .Location in patent: Page/Page column 57.
[2]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

8
[ 18113-07-0 ]
[ 106-93-4 ]
[ 26378-26-7 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

9
[ 18113-07-0 ]
[ 107-99-3 ]
[ 26378-43-8 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

10
[ 18113-07-0 ]
[ 100-35-6 ]
[ 26378-45-0 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

Yield	Reaction Conditions	Operation in experiment
		PREPARATION M12 4-Chloro-3-methoxyphenol The product of the preceding Preparation (8.2 g, 0.052 mol) was dissolved in 50 ml concentrated H2 SO4 by stirring and warming. The solution was cooled and slowly and carefully diluted, with stirring, with 50 ml H2 O (reverse addition is preferred). At 0, NaNO2 (3.8 g, 0.055 mol) in 10 ml H2 O was added dropwise. The mixture was slowly warmed to room temperature, stirred for 15 minutes, then warmed to 50 C. until gas evolution ceased. The mixture was cooled, diluted with an equal volume of water, saturated with excess NaCl and extracted with an equal volume of ether. The ether extract was dried over MgSO4, stripped to an oil and chromatographed on 250 cc silica gel with CHCl3 as eluant to yield purified title product, 1.7 g, having 1 H-NMR consistent with its structure, used as starting material for Preparation L1, above.

12
[ 75-11-6 ]
[ 18113-07-0 ]
[ 403657-31-8 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; water;	bis(4-chloro-3-methoxyphen-1-oxy)methane) A solution of 100 g of <strong>[18113-07-0]4-chloro-3-methoxyphenol</strong> in 250 ml of dimethylformamide was slowly added dropwise to a suspension of 16.0 g of sodium hydride (95% strength) in 300 ml of dimethylformamide under argon at 0 C. When the addition was complete, the mixture was after-stirred for a further 1 hour at 40 C., giving a clear, yellow solution. At room temperature, a solution of 88.1 g of diiodomethane in 100 ml of dimethylformamide was then slowly added dropwise. The solution was stirred for 15 hours at room temperature, during which an orange-red suspension gradually formed. The mixture was then stirred for a further 3 hours at 50 C. 400 ml of water were added and the mixture was extracted with 3150 ml of methylene chloride. The combined organic phases were washed with 3100 ml of saturated aqueous sodium chloride solution, the organic phases were dried over sodium sulfate, and the solvent was removed at 50 C. under reduced pressure, giving an orange-brown solid residue. This residue was dissolved in 250 ml of methyl tert-butyl ether at the boil, decanted off from the oily residue present and concentrated by evaporation until precipitation occurred. The mixture was left to crystallize first at room temperature and then, to complete the precipitation, at +40C. The precipitate was filtered off and carefully washed with 1:1 methyl tert-butyl ether/petroleum ether. The mother liquor was concentrated by evaporation and left to crystallize again. Yield: 85.2 g (82% of theory) Melting point: 110 C. By removing the DMF prior to work-up with dichloromethane/water, it is possible to increase the chemical yield from 82 to 90%.

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.
[2]Patent: US2002/55653,2002,A1 .

13
[ 18113-07-0 ]
6,6'-bis-[bis-(2,4-dimethyl-phenyl)-phosphanyl]-3,3'-dichloro-2,2'-dimethoxy-biphenyl [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.

14
[ 18113-07-0 ]
[ 403657-32-9 ]

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.

15
[ 18113-07-0 ]
5,5'-dichloro-6,6'-dimethoxy-biphenyl-2,2'-diol [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.

16
[ 18113-07-0 ]
trifluoro-methanesulfonic acid 5,3'-dichloro-6,2'-dimethoxy-6'-trifluoromethanesulfonyloxy-biphenyl-2-yl ester [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.

17
[ 18113-07-0 ]
C₃₀H₂₂Cl₂O₆P₂ [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.

18
[ 18113-07-0 ]
(R)-(+)-5,5’-dichloro-2,2’-bis(diphenylphosphino)-6,6’-dimethoxy-1,1’-biphenyl [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.

19
[ 18113-07-0 ]
6,6'-bis-[bis-(4-fluoro-phenyl)-phosphanyl]-3,3'-dichloro-2,2'-dimethoxy-biphenyl [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.

20
[ 18113-07-0 ]
6,6'-bis-[bis-(2,5-dimethoxy-phenyl)-phosphanyl]-3,3'-dichloro-2,2'-dimethoxy-biphenyl [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2004,vol. 346,p. 979 - 982.

21
[ 18113-07-0 ]
[ 111478-41-2 ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2169 - 2177.

22
[ 18113-07-0 ]
[ 111477-57-7 ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2169 - 2177.
[2]Journal of Medicinal Chemistry,1992,vol. 35,p. 2169 - 2177.

23
[ 18113-07-0 ]
[ 111477-56-6 ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2169 - 2177.
[2]Journal of Medicinal Chemistry,1992,vol. 35,p. 2169 - 2177.

24
[ 18113-07-0 ]
[ 26378-41-6 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

25
[ 18113-07-0 ]
[ 26378-47-2 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

26
[ 18113-07-0 ]
[ 26378-49-4 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

27
[ 18113-07-0 ]
[ 26378-51-8 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

28
[ 1009-36-5 ]
[ 18113-07-0 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

29
2-methoxy-4-nitrobenzene diazonium 1,5-naphthalene disulfonate [ No CAS ]
[ 18113-07-0 ]

References: [1]Chimica Therapeutica,1969,vol. 4,p. 334 - 343.

30
[ 288-32-4 ]
[ 18113-07-0 ]
[ 181648-42-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	In N,N-dimethyl-formamide;	a) tert-Butyl-(4-chloro-3-methyl-phenoxy)-dimethyl-silane Under argon, tert-butyldimethylchlorosilane (1.21 g, 7.71 mmol) was added to a solution of <strong>[18113-07-0]4-chloro-3-methoxyphenol</strong> (1.0 g, 7.01 mmol) and imidazole (1.049 g, 15.42 mmol) in DMF (15 ml) at 0 C. After the addition, the ice bath was removed and the reaction mixture was stirred overnight. The solution was quenched with water and extracted with diethyl ether. The organic extract was washed with 2N HCl, water, aq. NaHCO3, brine then dried (Na2SO4). Removal of all volatiles in vacuo afforded the title compound as a colorless oil (1.73 g, 96%). Mass spectrum ES+: 257.0 [M+H]+.

References: [1]Patent: US2003/220392,2003,A1 .

31
[ 912342-70-2 ]
[ 18113-07-0 ]
2-(4-chloro-3-methoxyphenoxymethyl)-1-(3,5-dichlorobenzyl)-1H-imidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%		To a mixture of 2-chloromethyl-l-(3,5-dichlorobenzyl)-lH-imidazole hydrochloride (see Example 1) (150 mg, 0.5 mmol), <strong>[18113-07-0]4-chloro-3-methoxyphenol</strong> (158 mg, 1 mmol) and DMSO (1 mL) was added K2CO3 (415 mg, 3 mmol). The reaction was stirred at ambient temperature for 8 h before diluting with water (10 mL). A solution of IN HCl was added until the mixture was only slightly basic (pEta 8) before extracting with EtOAc (30 mL). The EtOAc phase was washed with water (10 mL), dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 1 :2, hexanes/EtOAc) to afford the title compound (194 mg, 97%) as a white solid: ESI MS m/z 397 [C18H15Cl3N2O2 + H]+.

References: [1]Patent: WO2006/107923,2006,A1 .Location in patent: Page/Page column 57; 58.

32
[ 107-93-7 ]
[ 18113-07-0 ]
[ 111478-41-2 ]

Yield	Reaction Conditions	Operation in experiment
	In methane sulfonic acid; chloroform;	PREPARATION L1 6-Chloro-7-methoxy-2-methylchroman-4-one A solution of 1.0 g (6.3 mmol) <strong>[18113-07-0]4-chloro-3-methoxyphenol</strong> and 5.4 g (6.3 mmol) crotonic acid in 15 ml methane sulfonic acid was heated at 95 C. under nitrogen for 20 hours. The reaction was cooled to 23 C., poured onto 150 ml ice and water and extracted with 100 ml ethyl acetate. The ethyl acetate extract was successively washed with 100 ml water, 2*100 ml 1N sodium hydroxide and 100 ml brine, dried over magnesium sulfate and concentrated in vacuo to a purple crystalline solid. This was purified by flash chromatography on 150 cc silica gel using chloroform as eluant to give the product as a yellow crystalline solid, 1.1 g (78%); m.p. 96-100 C. 1 H-NMR(CDCl3)delta(ppm): 7.65 (s, 1H), 6.32 (s, 1H), 4.45 (m, 1H), 3.80 (s, 3H), 2.48 (d, 2H), 1.42 (d, 3H) (substantially the same as the product of Preparation H1, above).
	In methane sulfonic acid; chloroform;	PREPARATION L1 6-Chloro-7-methoxy-2-methylchroman-4-one A solution of 1.0 g (6.3 mmol) <strong>[18113-07-0]4-chloro-3-methoxyphenol</strong> and 5.4 g (6.3 mmol) crotonic acid in 15 ml methane sulfonic acid was heated at 95C. under nitrogen for 20 hours. The reaction was cooled to 23C., poured onto 150 ml ice and water and extracted with 100 ml ethyl acetate. The ethyl acetate extract was successively washed with 100 ml water, 2 * 100 ml 1 N sodium hydroxide and 100 ml brine, dried over magnesium sulfate and concentrated in vacuo to a purple crystalline solid. This was purified by flash chromatography on 150 cc silica gel using chloroform as eluant to give the product as a yellow crystalline solid, 1.1 g (78%); m.p. 96-100C. 1H-NMR(CDCl3)delta(ppm): 7.65 (s, 1H), 6.32 (s, 1H), 4.45 (m, 1H), 3.80 (s, 3H), 2.48 (d, 2H), 1.42 (d, 3H) (substantially the same as the product of Preparation H1, above).

References: [1]Patent: US4853410,1989,A .
[2]Patent: EP230379,1991,B1 .

Yield	Reaction Conditions	Operation in experiment
		PREPARATION M12 4-Chloro-3-methoxyphenol The product of the preceding Preparation (8.2 g, 0.052 mol) was dissolved in 50 ml concentrated H2SO4 by stirring and warming. The solution was cooled and slowly and carefully diluted, with stirring, with 50 ml H2O (reverse addition is preferred). At 0, NaNO2 (3.8 g, 0.055 mol) in 10 ml H2O was added dropwise. The mixture was slowly warmed to room temperature, stirred for 15 minutes, then warmed to 50C. until gas evolution ceased. The mixture was cooled, diluted with an equal volume of water, saturated with excess NaCl and extracted with an equal volume of ether. The ether extract was dried over MgSO4, stripped to an oil and chromatographed on 250 cc silica gel with CHCl3 as eluant to yield purified title product, 1.7 g, having 1H-NMR consistent with its structure, used as starting material for Preparation L1, above.

34
[ 50-00-0 ]
[ 18113-07-0 ]
[ 89938-56-7 ]

References: [1]Tetrahedron Letters,2009,vol. 50,p. 6339 - 6341.
[2]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3530 - 3540.

35
C₁₃H₁₁ClO₄S [ No CAS ]
[ 18113-07-0 ]

References: [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3530 - 3540.

36
[ 18113-07-0 ]
[ 704882-50-8 ]

References: [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3530 - 3540.

37
[ 18113-07-0 ]
[ 1309612-64-3 ]

References: [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3530 - 3540.

38
[ 18113-07-0 ]
[ 1309612-66-5 ]

References: [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3530 - 3540.

39
[ 95-88-5 ]
[ 18113-07-0 ]

References: [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3530 - 3540.

40
4-chloro-3-methoxyphenyl 4-methylbenzenesulfonate [ No CAS ]
[ 18113-07-0 ]

References: [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 3530 - 3540.

41
[ 931410-10-5 ]
[ 18113-07-0 ]
5-[3-(4-chloro-3-methoxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanenitrile [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6888 - 6904.

42
[ 18113-07-0 ]
[ 693-02-7 ]
2-n-butylbenzo[b]furan-6-ol [ No CAS ]

References: [1]Journal of Organic Chemistry,2012,vol. 77,p. 6473 - 6479.

43
[ 95-88-5 ]
[ 74-88-4 ]
[ 18113-07-0 ]
[ 7051-13-0 ]

References: [1]Journal of Organic Chemistry,2012,vol. 77,p. 6473 - 6479.

44
C₇H₈Cl₂O₂ [ No CAS ]
[ 18113-07-0 ]

Yield	Reaction Conditions	Operation in experiment
144 mg	With lithium hexamethyldisilazane; In tetrahydrofuran; at -78 - 22℃; for 0.333333h;Inert atmosphere;	General procedure: An oven-dried 50mL round bottom flask equipped with a magnetic stirring bar was sealed with a rubber septum and then evacuated and backfilled with nitrogen (three cycles). The flask was charged with substrate ketone (1.00mmol, 1.00equiv), hexamethylphosphoramide (HMPA, 435muL, 448mg, 2.50mmol, 2.50equiv), and dry THF (5mL) and then cooled to 0C in an ice/water bath. A solution of LiHMDS (1.00M in THF, 3.00mL, 3.00equiv) was added dropwise over 3min. After stirring the mixture for 1h, the reaction system was cooled to -78C. A solution of tosyl halide (2.10mmol, 2.10equiv) in THF (3.0mL, then the vial was rinsed with 1.0mL and added to the reaction) was added dropwise over 10min. After 30min at -78C, a solution of LiHMDS (1.00M in THF, 1.00mL) was added dropwise over 1min. When the addition was complete, the mixture was warmed to room temperature over 20min at which time TLC indicated complete consumption of the dihalogenated intermediate (Rf?0.3 in 4:1 hexanes/EtOAc, visualized with p-anisaldehyde stain). The reaction was quenched with a saturated aq NH4Cl solution (10mL) and then EtOAc (20mL) was added. The phases were separated and the aqueous phase was then extracted with EtOAc (3×10mL). The combined organic phases were washed with brine (1×20mL), dried over anhyd Na2SO4, filtered through cotton, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford the desired product.

References: [1]Tetrahedron,2016,vol. 72,p. 3653 - 3665.

45
[ 18113-07-0 ]
C₁₅H₂₁NO₅S [ No CAS ]
C₂₂H₂₆ClNO₆S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 2446 - 2449.

46
[ 18113-07-0 ]
C₁₅H₂₁NO₅S [ No CAS ]
C₂₀H₂₂ClNO₆S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 2446 - 2449.

47
[ 18113-07-0 ]
2-(4-chloro-3-methoxyphenoxy)acetic acid [ No CAS ]

References: [1]Patent: WO2017/193034,2017,A1 .
[2]Patent: WO2019/90069,2019,A1 .

48
[ 18113-07-0 ]
2-(4-chloro-3-fluorophenoxy)-N-{3-[2-(4-chloro-3-methoxyphenoxy)acetamido]bicyclo[1.1.1]pentan-1-yl}acetamide [ No CAS ]

References: [1]Patent: WO2017/193034,2017,A1 .
[2]Patent: WO2019/90069,2019,A1 .

49
[ 5292-43-3 ]
[ 18113-07-0 ]
tert-butyl 2-(4-chloro-3-methoxyphenoxy)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In N,N-dimethyl-formamide; at 65℃; for 2h;	Example 27A : tert-butyl 2-(4-chloro-3-methoxyphenoxy)acetate [0824] A solution of <strong>[18113-07-0]4-chloro-3-methoxyphenol</strong> (lg, 6.31 mmol) in N,N-dimethylformamide (10 mL) was treated with tert-butyl 2-bromoacetate (1.024 mL, 6.94 mmol) and potassium carbonate (1.743 g, 12.61 mmol) and heated at 65 C for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with water twice. The organic extract was dried (Na2SC>4), filtered and concentrated to provide 1.72 g (100%) of the title compound. MS (APCI) m/z 273 (M+H)+.
100%	With potassium carbonate; In N,N-dimethyl-formamide; at 65℃; for 2h;	A solution of <strong>[18113-07-0]4-chloro-3-methoxyphenol</strong> (lg, 6.31 mmol) in N,N-dimethylformamide (10 mL) was treated with teri-butyl 2-bromoacetate (1.024 mL, 6.94 mmol) and potassium carbonate (1.743 g, 12.61 mmol) and heated at 65 C for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with water twice. The organic extract was dried (Na2SO/t), filtered and concentrated to provide 1.72 g (100%) of the title compound. MS (APCI) m/z 273 (M+H)+.

References: [1]Patent: WO2017/193034,2017,A1 .Location in patent: Page/Page column 241.
[2]Patent: WO2019/90069,2019,A1 .Location in patent: Page/Page column 269.

50
[ 18113-07-0 ]
[ 17417-09-3 ]
C₁₄H₉ClN₂O₄ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 10231 - 10244.

51
[ 18113-07-0 ]
N-(4-(N-(4-(4-chloro-3-methoxyphenoxy)-3-cyanophenyl)sulfonamido)phenyl)acetamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 10231 - 10244.

52
[ 18113-07-0 ]
5-amino-2-(4-chloro-3-methoxyphenoxy)benzonitrile [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 10231 - 10244.

53
[ 18113-07-0 ]
2-(4-chloro-3-fluorophenoxy)-N-{(3S)-4-[2-(4-chloro-3-methoxyphenoxy)acetamido]-3-hydroxybicyclo[2.2.2]octan-1-yl}acetamide [ No CAS ]

References: [1]Patent: WO2019/90069,2019,A1 .

54
[ 95-88-5 ]
[ 74-88-4 ]
[ 18113-07-0 ]

Yield	Reaction Conditions	Operation in experiment
46%		To a stirred solution of 4-chlororesorcinol (4.0 g, 27.67 mmol) in acetone (100 mL) was added potassium carbonate (7.40 g, 53.50 mmol). The mixture was stirred 30 minutes at room temperature and iodomethane (1.72 mL, 27.67 mmol) was added dropwise. The resulting solution was stirred at reflux for 18 h. The mixture was concentrated in vacuo before, hydrolyzed with a saturated aqueous solution of NH4Cl, extracted using ethyl acetate, the organics were washed with brine, dried over MgSCL and concentrated in vacuo before purification by silica gel flash chromatography eluting with a gradient of cyclohexane:ethyl acetate - 100:0 to 80:20 to give the title compound as a beige solid (2.0 g, 46% yield). ESIMS m/z [M+H]+=l59.0.

References: [1]Patent: WO2020/65,2020,A2 .Location in patent: Page/Page column 97-98.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Nomenclature of Ethers • Preparation of Alkylbenzene • Preparation of Ethers • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Ethers • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Vilsmeier-Haack Reaction

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H250	Catches fire spontaneously if exposed to air
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CAS No.: 18113-07-0

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CAS No.: 18113-07-0

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[ 18113-07-0 ] Synthesis Path-Downstream 1~54

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